Abstract
The influence of dose on thein vitro metabolism of indomethacin has been investigated in four laboratory species (rat, rabbit, guinea pig, hamster). It was found that in the rat and guinea pig the ratio of deacylated to demethylated metabolites was dependent on the substrate concentration of indomethacin, whereas in the rabbit the ratio remained constant in the dosage range investigated (1–10 μmoles). No demethylated product was found in the hamster but a high level of activity of the deacylase enzyme was observed. These findings may help to explain species-dependent toxicity.